PROJECT SUMMARY/ABSTRACT The investigation of new drug therapies depends on simple, consistent, cheap, and versatile synthetic approaches which can deliver a broad array of drug-like molecules for expedient evaluation and diversification. Many biologically active molecules contain complex stereodefined functionalized rings, and therefore, developing new methods which can build molecular complexity into rings is attractive. One strategy for accomplishing this goal is to transform saturated heterocycles or monosubstituted rings by C?H functionalization reactions which exchange highly abundant C?H bonds for new, desirable C?C bonds. This strategy is challenging because of the relative abundance of seemingly indistinguishable C?H bonds, and therefore, chemists strive to address this difficulty by implement directing groups, site-selective catalysts, and even substrate bias to successfully react the desired C?H bonds. Additionally, the functionalization of saturated heterocycles or monosubstituted rings introduces setbacks associated with stereoselectivity because functionalization of certain C?H bonds induces desymmetrization which escalates rapidly the number of products which can be generated if selectivity is low. This proposal describes how these challenges will be addressed by developing new catalytic organometallic transformations in two projects. The first project will utilize silacycloalkanes as targets for C?H functionalization reactions with dirhodium tetracarboxylate catalysts using carbenes derived from diazo precursors. The preliminary explorations in this area have unveiled the utility of a new bulky dirhodium catalyst whose reactivity is largely unexplored. The use of diazo precursors will permit the incorporation of a variety of heteroaromatic donors which are highly desired in pharmaceutical agents. This work will generate a variety of substituted silacycloalkanes which occupy unprecedented chemical space, and therefore, the new compounds will be submitted to the on-campus high- throughput testing facility. In addition, the silacycloalkanes will be transformed to synthetically attractive diols. The second project will address whether catalytic systems can be generated which allow the functionalization of different C?H bonds on the same basic scaffold. Most studies in dirhodium catalyzed C?H functionalization chemistry rely on inherent substrate bias for achieving site selectivity, but recent developments now suggest this inherent bias can be overcome by exploiting different catalysts. This prompts whether catalytic systems can be devised which enable the functionalization of specific C?H bonds at will. Protected cyclohexanol will serve as the test substrate for these studies. By altering the protecting group on the oxygen, the diazo precursor, and the catalyst, the selectivity of the reaction will be explored, and new catalytic systems will be devised which can selectively functionalize different C?H bonds on the same parent molecule.